Project Summary: Non-invasive functional imaging of the healthy adult human brain has enabled mapping of the spatial and temporal organization of brain functions and revolutionized cognitive neuroscience. Increasingly, functional neuroimaging is being used as a diagnostic and prognostic tool in the clinical setting and to view brain development. Its expanding application in the study of disease and development necessitates new, more flexible functional neuroimaging tools. Many situations are not suitable to MRI scanner logistics, such as subjects who are in an intensive care unit or subjects who might otherwise require sedation for imaging, such as infants and young children. Furthermore, traditional functional neuroimaging methods use behavioral paradigms not suited to these same subject groups. Young children cannot attend to many tasks, and unconscious patients in the operating room or intensive care cannot reliably perform tasks. Diffuse optical imaging (DOI), an emerging, non-invasive technique with unique portability and hemodynamic contrast capabilities, can record evoked brain function in enriched or clinical environments. However, despite unique strengths, DOI as a standard tool for functional mapping has been limited by low spatial resolution, limited depth penetration, and a lack of reliable and repeatable mapping. Though DOI of brain activity is commonly performed using topography with sparse imaging arrays, high-density arrays and tomography algorithms provide a means to dramatically increase image quality. In addition to image quality restrictions, previous DOI has employed restrictive task-based behavioral paradigms. An alternate method, recently explored with fMRI, uses temporal correlations in the resting state fluctuations between different brain regions to spatially map functional connections. The goal of this grant is to develop DOT methods for mapping resting state functional connectivity in order to study the childhood development of brain functions. We recently demonstrated the feasibility of a DOT prototype that solves several basic challenges in inter-channel cross talk and enables tomography of the adult visual cortex (Zeff et. al. PNAS 2007). To meet the additional demands mapping extended brain function networks in humans, this grant will achieve three development goals: first, we will develop a second generation instrument with the necessary improvements in depth penetration, cortical coverage, and cap wear-ability; second, we will create algorithms for projecting DOT maps of cerebral hemoglobin into a reference atlas space and third we will develop methods for determining function connectivity in the resting state. These technical developments will be validated in adults within whom comparisons can be made to detailed evoked responses and to fMRI. These steps will establish a strong foundation for applying DOT to study how brains function in young children; a question not readily addressed with current neuroimaging techniques.